Annexins are a family of some 10 structurally related proteins found in diverse eukaroytic organisms such as fruit fly, sponges, slime molds, higher plants, and mammals (Towle, C. A. and Treadwell, B. V. (1992) J. Biol. Chem. 267:5416-23). Proteins in this family reversibly bind to negatively charged phospholipids (phosphatidylcholine and phosphatidylserine) in a calcium dependent manner. Many of the functions attributed to annexins are believed to be the result of this binding property. These functions include; (1) regulation of phospholipase A2 activity, (2) anticoagulant activity, (3) roles in cellular exocytosis, (4) membrane trafficking, (5) cytoskeletal organization, (6) phosphohydrolase activity, (7) various aspects of cell proliferation, and (8) calcium channel activity (Towle et al. supra).
Annexin V is a specific family member found in a variety of species including human. It is widely distributed in various cells and tissues and is particularly abundant in brain, where it is believed to act as a paracrine-type neurotrophic factor (Ohsawa, K. et al. (1996) J. Neurochem. 67:89-97). It is also known to possess anticoagulant activity, transport Ca.sup.2+ ions across phospholipid membranes, and inhibit phospholipase A2 and protein kinase C.
Various proteins bind members of the annexin family and are implicated in mediating their activity. These include several cytoskeletal proteins such as actin, calspectin, synapsin I, and glial fibrillary protein. In an attempt to elucidate the mechanism underlying neurotrophic activity in rat brain, Oshawa et al. (supra) sought and found four specific annexin binding proteins, ABP-2, ABP-4, ABP-7, and ABP-10. They also demonstrated that Ca.sup.2+ and phospholipid were necessary for maximum binding to occur.
No common binding motifs were found among the four proteins; however, all four proteins were highly hydrophilic, showed no hydrophobic regions, and contained high proportions (10-20%) of lysine, glutamate, and serine. Arginine or aspartate was also prevalent in three of the four proteins. Some or all of these common properties may be asocciated with annexin binding.
In addition, two of the proteins, ABP-2 and ABP-4, each demonstrated high homlogy with the known human proteins, X-linked helicase (XH2) and DNA methyltransferase (DMTase), respectively. XH2 is a transcriptional regulator the mutations of which affects the expression of several genes and results in a form of X-chromosome linked mental retardation (Gibbons, R. J. et al. (1995) Cell 80:837-845). Helicases such as XH2 are involved in a variety of cellular functions including mitotic chromosome segregation, DNA recombination and repair, and regulation of transcription. DMTase is also a key enzyme in controlling gene expression and regulating cell differentiation and maturation (Ohsawa et al. supra).
The discovery of a new annexin binding protein and the polynucleotides encoding it satisfies a need in the art by providing new compositions which are useful in the diagnosis, prevention and treatment of cancer, immune disorders, and neurological disorders.